p21-activated kinase signalling in pancreatic cancer: New insights into tumour biology and immune modulation

Figure 2 Role of p21-activated kinases in Kras-driven oncogenic signalling pathways. Rac1 is the 4^th best validated effector in Kras signalling and is a well-defined upstream protein of PAKs. Rac1 plays an important role in the ADM/PanIN/PDAC transition. In addition, Rac1/Cdc42 mediates this pathological process via the PI3K-PDK1 signalling pathway. PDK1 can also interact with PAK1, leading to its phosphorylation. The Kras oncogene activates PAKs through direct and indirect pathways. Activated PAKs can increase cancer cell proliferation, migration and survival through activation of AKT, Crk and RAF-MEK-ERK pathways. PAK: p21-activated kinases; ADM: Acinar-ductal metaplasia; PDAC: Pancreatic ductal adenocarcinoma; PDK1: Phosphoinositide-dependent kinase-1.